The present invention relates to a system and method for monitoring a patient for rejection of an implanted organ. More particularly, the system and method of the present invention relate to a telemetry monitoring unit, implanted within the body of a patient which includes an activatable acoustic transducer energizable by an acoustic signal provided from outside the body, such that rejection reactions of an implanted organ such as, for example, an implanted heart, kidney, lung or liver can be monitored and thereby detected as early as possible, while lesser damage has been inflicted upon the transplanted organ, and while immunosuppressive therapy can be most efficiently applied.
Repeated monitoring of physiological parameters associated with certain medical conditions presented by a patient is crucial for effective and timely treatment of such disorders and conditions.
For example, following organ transplantation, rejection of the transplanted organ, especially of a transplanted heart, is a substantial problem often encountered in surgical transplant procedures. As such, it is important to frequently monitor the transplanted organ of the recipient, so as to diagnose a rejection reaction as early as possible in order to be able to institute timely immunosuppressive therapy.
In addition, procedures such as invasive endomyocardial biopsy also neccesitate and employ constant monitoring, often achieved via implantation of hardwire electrodes.
Due to the nature of these medical conditions and further due to limitations inherent to external monitoring devices, implanted monitoring devices are preferably employed in monitoring these conditions. These devices which can be for example, hardwire electrodes, or telemetry devices, relay information pertaining to the condition or disorder to an analysis and recording device positioned outside the body.
Several such telemetry devices which provide information pertaining to physiological parameters associated with medical conditions have been described in the prior art.
For example an implantable telemetry pacemaker, which transmits measured values via an inductive coupling to extracorporeal instruments, see, for example, U.S. Pat. Nos. 4,809,697; 4,585,004; 4,237,900; 4,550,370; and 4,281,664, is used as an implanted monitoring device. These telemetry pacemakers permit repeated monitoring of a patient, by monitoring and measuring electrocardiac rhythms at selected time intervals. In addition, by employing telecommunication systems or by providing a small extracorporeal recording device carried by the patient, monitoring can be effected outside the medical facility.
When using a pacemaker telemeter device as described above, intramyocardial measurements, as effected for example, on a transplanted heart, are oftentimes unreliable since measured results are often influenced by for example, variations of daily electrocardiac rhythm, the exertion state of the patient and the medication ingested by the patient. Thus a drop of the measured cardiac voltage signals is not necessarily due to, and indicative of, an incipient rejection reaction.
An example of a more accurate system for monitoring a transplanted organ is disclosed in U.S. Pat No. 5,246,008 which describes a battery powered measuring system implanted on the monitored organ for providing data, as electromagnetic radiation, relating to the electrophysiological condition of the organ. The disclosed system is based on the knowledge that functional changes of organs and especially functional changes of the heart are associated with changes of the electrophysiological properties of the tissue, which changes can be detected by a change of the electrical impedance of the tissue (see, for example, B. C. Penney et al., Medical & Biological Engineering & Computing, 1985, 23, p. 1-7; Pfitzmann R, Muller J, Grauhan O. Cohnert T, Hetzer R, Z Kardiol, 1998, Measuring bioelectric myocardial impedance as a non invasive method for diagnosis of graft rejection after heart transplantation, 87(4):258-266; Hetzer R. et al., 1998, Daily non-invasive rejection monitoring improves long-term survival in pediatric heart transplantation, Ann. Thorac. Surg. (66):1343-1349; Pirolo J S, Shuman T S, Brunt E M, Liptay M J, Cox J L, Ferguson T B Jr., J Thorac Cardiovasc Surg, 1992, Non invasive detection of cardiac allograft rejection by prospective telemetric monitoring, 103(5):969-79; Bonnefoy E, Ninet J, Robin J, Leroux F, Boissonat P, Brule P, Champsaur G., 1994, Bipolar intramyocardial electrogram from an implanted telemetric pacemaker for the diagnosis of cardiac allograft rejection, Pacing Clin Electrophysiol, 17(11 Pt 2):2052-6; Gerhausser A, Reichel T, Neukomm P A, Bolz A, Hugel J, Schaldach M, 1997, Diagnosis of rejection after kidney transplantation by impedance spectroscopy with an implantable measuring system, Biomed Tech (Berl), 42 Suppl. 160-1, which are incorporated herein by reference).
The electrical impedance is a complex variable having both amplitude and phase. For a given alternating voltage, V, of the form: EQU V=A.multidot.e.sup.i.omega.
the resulting current, I, is: EQU I=B.multidot.e.sup.i(.omega.t-.phi.)
where A and B are the voltage and current amplitude, respectively, .omega. is the frequency, i is the square root of -1, t is time and .phi. is the relative phase between the voltage and the current.
The electrical impedance, Z, is defined as: EQU Z.tbd.V/I
or more specifically as: EQU Z=.vertline.Z.vertline..multidot.e.sup.i.phi.
where .vertline.Z.vertline..tbd.A/B is the absolute value of the electrical impedance.
It is believed that the changes in electrical impedance are due to interstitial edemas, infiltration in the interstitial tissues and electrophysiological changes of the cell membranes and of their resistive and capacitive properties.
Although measuring tissue impedance is considered a more accurate method to predict heart tissue rejection, accurate and efficient monitoring using the above described system is impeded by several limitations due to the utilization thereby of electromagnetic radiation to establish telemetry between the implanted monitor and an extracorporeal controlling and recording device.
Since the electromagnetic radiation transmitted into the body by an extracorporeal unit of this system does not supply sufficient power to energize the implanted monitor, a battery is included within the implanted monitor.
In addition, since electromagnetic radiation does not penetrate body tissues well, this system necessitates additional electrical leads which are wire connected to the monitoring device and implanted close to the body surface for receiving the electromagnetic radiation and relaying it to the implanted monitor. This power manifestation drastically decreases the time period for which the device can be employed within the body since batteries are exhaustible. In addition since this system necessitates implantation of two interwired components in different locations of the body, the implantation procedure is rendered complicated and the chances of infection are increased.
Moreover, since the prior art devices require electrical wires for energy supply and communication, it is not practical to implant such devices deep within an organ. Since some physiological changes are initiated deep within the organ, remote from its surface, it is advantageous to measure the impedance deep within in the transplanted organ.
There is thus a widely recognized need for, and it would be highly advantageous to have, a system and method for monitoring a patient for rejection reactions of an implanted organ devoid of the above limitations, which system is implanted power source free and has further advantages as further detailed hereinunder.